guidelines on variations to a registered pharmaceutical product

Guidelines on Variations to a Registered Pharmaceutical ProductDocumentation required1. A declaration from the supplier of the FPP that the route of synthesis, quality control procedures andspecifications of the API and key (ultimate) intermediate in the manufacturing process of the API (ifapplicable) are the same as those already accepted.2. Name, address, and responsibility of the proposed production site or facility involved in manufacturingand/or testing (including block(s) and unit(s). A valid manufacturing and/or testing authorization and acertificate of GMP compliance, if available.3. Description of the batches, copies of certificates of analysis and batch analysis data (in a comparativetabular format) for at least two (minimum pilot scale) batches of the API from the currently acceptedand proposed units/blocks.4. A summary of differences between manufacture and control of the API at the currently accepted andproposed units/blocksDescription of changeConditions to befulfilledDocumentationto be suppliedReportingtype12a change in the manufacturing process of the 1-3 1-2, 8 AN12bactive pharmaceutical ingredient1-2, 4, 6-9 3-4, 11-12 IN12c 1-2, 4-7 3-4, 11-12 Vmin12d None 2-14 VmajConditions to be fulfilled1. No change in the physical state (e.g. crystalline, amorphous) of the API.2. For low solubility APIs, there is no change in the polymorphic form and whenever particle size is critical(including low solubility APIs) there is no significant change in the particle size distribution comparedto the API lot used in the preparation of the biobatch.3. API manufacturing site is currently accepted through the WHO PQP APIMF procedure.4. Where materials of human or animal origin are used in the process, the manufacturer does not use anynew process for which assessment of viral safety data or TSE risk assessment is required.5. No change in the route of synthesis (i.e. intermediates remain the same) and there are no newreagents, catalysts or solvents used in the process.6. No change in qualitative and quantitative impurity profile or in physicochemical properties of the API.7. The change does not affect the sterilization procedures of a sterile API.8. The change involves only steps before the final intermediate.9. The change does not require revision of the starting material, intermediate or API specificationsDoc. No.: DAR/GDL/005 Revision Date: 8 th July 2013 Review Due Date: 16 th July 2016Revision No.: 1 Effective Date : 16 th July 2013 Page 21 of 70